The product of the herpes simplex virus type 1 (HSV 1) UL49 gene, the structural protein VP22 (Elliott et al, J. Gen. Virol., 73:723–6), is a major component of the HSV tegument, a compartment of the virion located outside the capsid and inside the envelope and composed of at least 10 or more additional virus polypeptides. VP22 has a molecular weight of 32 kD, is very basic and is modified by phosphorylation and nucleotidylation in the infected cell.
Despite being one of the major tegument proteins within the virion, together with the well characterised transcription regulatory protein VP16, much remains to be discovered about the function of VP22 during the virus replicative cycle. It is not yet known if it is an essential virus protein, but it is possible that, in a manner similar to VP16, VP22 has more than one role to perform during infection—initially as a functional protein during viral gene expression, and subsequently as a structural component of the virion during virus assembly. As regards the former, some evidence exists to suggest that VP22 can bind specifically to HSV 1 DNA.
In International patent application WO 97/05265 (O'Hare and Elliott) (incorporated herein by reference), it is disclosed inter alia that when the HSV 1 protein VP22 is expressed by transfection in mammalian cells, it exhibits a series of unusual properties. Firstly, the protein spreads between cells, so that when VP22 is expressed in a group of cells, it is secreted and delivered to the nuclei of other cells in the population not initially transfected. Secondly, in cells in which VP22 is expressed, it is present in a cytoplasmic filamentous pattern. The application further discloses that the transport property related to the secretion and delivery is associated with a determinant in the C terminal 34 amino acids of VP22. Applications of the transport property of VP22 disclosed in WO 97/05265 include associating molecules with VP22 so that they are transported to a target population of cells, either by expression of VP22, or an active fragment thereof, and the associated molecule as a fusion protein in some of the cells in the population, or by coupling VP22, or an active fragment thereof, to the associated molecule and exposing a population of cells to the VP22 complex directly.